Risk Of Radiation Necrosis Research Articles

BM-05 * IPILUMUMAB THERAPY FOR MELANOMA BRAIN METASTASES IS ASSOCIATED WITH INCREASED RADIATION NECROSIS

BACKGROUND: Melanoma brain metastases (MBMs) are typically associated with poor prognosis, requiring combination therapy with surgery and radiation. The CTLA-4 antagonist, ipilumumab, has shown improved survival in patients with MBMs. Herein, we present a series of patients treated with variable combinations of radiation, surgery and ipilumumab. METHODS: Over 4.5 years, all patients with symptomatic MBMs with at least one craniotomy for tumor resection and radiation therapy were included. The onset, duration and magnitude of radiation necrosis (RN) were analyzed relative to surgical resection, tumor size, and ipilumumab therapy. RN was based on pathology or imaging findings. Patients with less than 6 months follow-up were excluded. RESULTS: The cohort consisted of 59 patients (42 males,17 females,age 58 ± 14 years) with 154 metastatic tumors. 48 patients (81.4%) underwent adjuvant radiation therapy (74.6% SRS,22% WBRT). A total of 68 MBMs were resected in these patients (27.3 ± 11.6mm max dimension). Median overall and progression-free survival was 10.5 and 6.8 months respectively. 72% received ipilumumab therapy. Lesions receiving both SRS and WBRT had increased risk of RN compared to SRS or WBRT alone (38.5%v13.1%v9.1%,p = 0.003). Ipilumumab therapy was associated with increased RN (20.7%v4.7%,p = 0.015). Lesions that received ipilumumab following radiation were at higher risk of developing RN compared to ipilumumab preceding radiation (26.0%v16.4%,p = 0.023) with treatment interval 2.5v3.8 months. Overall, there was no significant difference in tumor size and rate of RN (28.2 ± 11.8v22.7 ± 12.2mm,p = 0.071). However, in patients who did not receive ipilumumab therapy, tumor size was significantly associated with RN (28.2 ± 11.8v19.2 ± 9.1mm,p = 0.010). Multivariate analysis demonstrated SRS in the absence of ipilumumab as an independent factor for RN. Surgical resection prior to radiation did not reduce RN rate (15.9%v23.7%,p = 0.312). CONCLUSION: This series demonstrates that ipilumumab independently increases the risk of RN for MBMs, particularly with SRS. Paradoxically, ipilumumab therapy following radiation had a higher rate of RN, suggesting an ongoing immune-mediated process in the radiated field.

BM-10 * SYSTEMIC TREATMENT AND RADIATION NECROSIS FOLLOWING GKSRS IN THE TREATMENT OF BRAIN METASTASES

INTRODUCTION: Based on anecdotal evidence from our institution, we sought to investigate the hypothesis that systemic therapy, and in particular newer immune therapy agents (IT) would increase the risk of developing radiation necrosis (RN) following stereotactic radiosurgery (SRS) with Gamma Knife (GK) for brain metastases (BM). METHODS: All patients undergoing GK at our institution between 2006 and 2012 were reviewed. 189 patients were identified of whom 183 survived more than 6 months. Details including type of systemic therapy (cytotoxic chemotherapy (CT), targeted therapy (TT) and immune therapy (IT) were recorded. Timing of ST in relation to GK was also recorded (before, during, less than 6 months and more than 6 months post GK). Logisitic regression was used to calculate the odds of developing RN by type of ST. RESULTS: Median follow up was 11.7 months. 42 patients (23%) developed RN of which 13 received IT alone. On univariate analysis, IT alone was associated with an increased risk of developing RN compared to CT alone (OR-2.44 [95%CI 1.02-5.79], p= 0.044) ) Multivariate analysis showed a trend towards an increased risk of RN with any IT (OR 1.9 {95%CI 0.91-3.99], p = 0.09) while receving any CT was found to be protective against RN (OR 0.39 [95% CI 0.19-0.79}, p = 0.009). CONCLUSION: Use of immune based therapies in patients receiving SRS for BM was associated with an increased risk of RN. Further investigation is needed to characterize these changes including to determine whether the increased rate of RN is due to a pro inflammatory effect of immune therapy or an interaction with radiation.

Delayed complications after Gamma Knife surgery for intractable epilepsy

Despite the controversy concerning the clinical usefulness of Gamma Knife surgery (GKS; Elekta AB, Stockholm, Sweden) for intractable epilepsy, this treatment modality has attracted attention due to its low invasiveness. We report the long-term outcomes of four patients, focusing particularly on the efficacy and complications of GKS. We reviewed the data of four patients with medically intractable epilepsy who underwent GKS between 1998 and 2000 at our hospital. The marginal dose to the 50% isodose line was 24Gy in one patient and 20Gy in the remaining three patients. Two of the four patients were treated in the right temporal lobe, one was treated in the left parietal lobe, and one was treated in the right frontal lobe. The mean follow-up was 12.5years (range 12–14years). One patient was seizure free (Engel class IA) 24months after GKS, and two patients failed to show any seizure reduction (Engel class IVA). However, a clear aggravation was evident in one patient (Engel class IVC). All four patients underwent resective surgery due to radiation necrosis (RN) 7, 10, 10 and 12years after GKS. Three patients were seizure free (Engel class IA), and one was considered to have Engel class IB status following the resective surgery. GKS treatment resulted in insufficient seizure control and carried a significant risk of RN after several years. Drawbacks such as a delay in seizure control and the risk of RN should be considered when the clinical application of this treatment is evaluated.

Cerebral radiation necrosis

Cerebral radiation-induced injury ranges from acute reversible edema to late irreversible radiation necrosis (RN). Cerebral RN is poorly responsive to treatment, is associated with permanent neurological deficits and occasionally progresses to death. We review the literature regarding cerebral RN after radiotherapy for various brain and head and neck lesions and discuss its clinical features, imaging characteristics, pathophysiology and treatment. For new enhancing lesions on computed tomography or magnetic resonance imaging, apart from tumor progression or recurrence, RN needs to be considered in the differential diagnosis. Further studies are required to design chemoradiotherapy protocols that are effective in treating tumors while minimizing risk of RN. Current available treatments for RN, steroid and surgery, only relieve the mass effect. None of the experimental treatments to date have consistently been shown to reverse the pathologic process of RN.

Impact of Concurrent and Adjuvant Bevacizumab on the Risk of Radiation Necrosis Following Radiosurgery for Recurrent Glioma

Bevacizumab has been identified as a potential treatment option for patients with radiation necrosis of the brain. The ability of bevacizumab to prevent radiation necrosis following reirradiation with stereotactic radiosurgery (SRS) has not been previously examined.

Safety and efficacy of concurrent interstitial radiation and hyperthermia in the treatment of progressive malignant brain tumors

High activity 125I brachytherapy has efficacy in selected recurrent malignant brain tumors, but limited efficacy and risk of radiation necrosis have prompted investigation of additional adjunctive therapies. This study aims to assess the toxicity of interstitial conductive hyperthermia used concurrently with 125I brachytherapy for the treatment of recurrent brain malignancies. Twelve patients with recurrent malignant brain tumors were implanted using afterloading catheters intended to deliver 50 Gy at the isodose line encompassing the enhancing tumor with a 5-mm margin and heated to 41.5 degrees C for 48 h. The average implant volume was 18 cc with 5.3 catheters containing 9.4 sources with a total activity of 265 mCi. Serious toxicities included 8 motor deficits, 2 mood alterations, 4 seizures and 2 catheter wound cerebrospinal fluid leaks. Median survival was 10.35 months with the best responses being 6 with stable disease and 2 with partial responses. Reoperation rate for radiation necrosis was 33%. Concurrent conductive thermoradiotherapy is feasible but is associated with serious toxicity. There is no suggestion of improved survival with thermoradiotherapy over brachytherapy alone. Given the degree of toxicity observed, alternative approaches to improving local control of these tumors are being explored.

Analysis of neurological sequelae from radiosurgery of arteriovenous malformations: How location affects outcome

To elucidate how the risks of developing temporary and permanent neurological sequelae from radiosurgery for arteriovenous malformations (AVM) are related to AVM location, the addition of stereotactic magnetic resonance (MR) imaging to angiographic targeting, and prior hemorrhage or neurological deficits. We evaluated follow-up imaging and clinical data in 332 AVM patients who received gamma knife radiosurgery at the University of Pittsburgh between 1987 and 1994. All patients had regular clinical or imaging follow-up for a minimum of 2 years (range: 24-96 months, median = 45 months). There were 83 patients with MR-assisted planning, 187 with prior hemorrhages, and 143 with prior neurological deficits. Symptomatic postradiosurgery sequelae (any neurological problem including headache) developed in 30 (9%) of 332 patients. Symptoms resolved in 58% of patients within 27 months with a significantly greater proportion (p = 0.006) resolving in patients with Dmin < 20 Gy vs. > or = 20 Gy (89 vs. 36%). The 7-year actuarial rate for developing persistent symptomatic sequelae was 3.8%. We first evaluated the relative risks for different locations to construct a postradiosurgery injury expression (PIE) score for AVM location. Multivariate logistic regression analysis of symptomatic postradiosurgery sequelae identified independent significant correlations with PIE location score (p = 0.0007) and 12 Gy volume (p = 0.008), but with none of the other factors tested (p > 0.3), including the addition of MR targeting, average radiation dose in 20 cc, prior hemorrhage, or neurological deficit. We used these results to construct a risk prediction model for symptomatic postradiosurgery sequelae. The risk of radiation necrosis was significantly correlated with PIE score (p < 0.048), but not with 12-Gy volume. The risks of developing complications from AVM radiosurgery can be predicted according to location with the PIE score, in conjunction with the 12-Gy treatment volume. Further study of factors affecting persistence of these sequelae (progression to radiation necrosis) is needed.

Statistical analysis of clinicopathological features, radiotherapy, and survival in 170 cases of oligodendroglioma.

The postoperative survival time of 170 nonrandomized patients treated for cerebral oligodendrogliomas in Norway from 1953 to 1977 was studied. Survival times were significantly prolonged if postoperative irradiation was performed in addition to surgery (median survival time 26.5 vs. 38 months, p = 0.039). In the group without postoperative radiotherapy, the 5-year rate of survival was 27% compared with 36% in the irradiated patients. The respective survival rates after 8 years were 14% versus 17%; thus, there was little effect on long-term survival. Irradiation appears not to be of benefit after "total" removal. Patients with partly resected lesions appeared to benefit from postoperative radiotherapy; the median survival period after subtotal tumor resection was 37 months with and 26 months without radiotherapy (p = 0.0089). The findings also indicate that irradiation doses between 40 and 50 Gy were as effective as doses between 50 and 60 Gy in increasing the patients' probability of surviving 5 years after subtotal tumor resection. Since the risk of radiation necrosis is proportional to the dose applied, the lower dose is recommended. These conclusions were also valid when adjustments were made for prognostically significant histological and clinical features.